There is an urgent need for devising and standardizing procedures for monitoring the effects of environmental mutagens on the genetic systems of higher animals. For practical purposes, these procedures should be relatively inexpensive, not laborious, easily quantitated, and the test objects should be related to the genetic system of man and other mammals. Chromosomes of cells in culture fulfill all these criteria and should be one of the most suitable testing materials. Since most mutagens induce chromosome damage (hence they are also clastogens), chromosome damage should serve as a conservative indicator of gene damage. However, investigators in the past used various test objects (many were poor materials) and test systems (many haphazardly designed), so their data are incomplete and are not strictly comparable. This project is designed to systematically test several cytologically advantageous materials and to determine the most efficient, economical and information-yielding protocol for future screening of environmental mutagens. Our test materials include, in addition to diploid human fibroblasts, cells of the Chinese hamster (for its fast growth rate and good chromosomes), the Indian muntjac (for its very low diploid number, 2n equals 6), two species of the deer mice (differing drastically in the amount of constitutive heterochromatin and repetitive DNA content), the laboratory mouse, and several other species. Test compounds will include well-known clastogens, probable clastogens and untested chemicals. The drug experiments will consist of continuous treatments (to determine inhibition of mitosis, stickiness, chromosome orientation, breaks and subsequent aberrations), aberrations in the recovery populations after pulse treatments, frequency of sister chromatid exchanges when the cells are treated with 5-bromodeoxyuridine in conjunction with test compounds, and other cytogenetic characteristics. Also, we plan to use chick embryos in vivo to test the possibility of using developing tissues for clastogen assays.